The objective of this project is to produce human antibodies and antibody hybrids in plants (plantibodies)) to meet the market needs (low cost, large capacity) of a vaginal microbicide for preventing the sexual transmission of human immunodeficiency virus (HIV). Since the mechanisms of sexual transmission of HIV are not well understood, plantibodies will be developed to a range of targets that individually or synergistically may provide protection against mucosal HIV transmission. Several well-studied monoclonal antibodies to gp160 (2F5, 2G12, 4E10) that have demonstrated broad neutralizing activity in vitro against primary isolates and protection in primates will be produced in plants. Since plantibody hybrids may be less susceptible to gp160 variability or epitope accessibility, two hybrids will be manufactured in plants: (a) PRO542 which has CD4 replacing the binding domain of the antibody scaffold; (b) sCD4-17b (CD4 linked to an HIV scFv) causes a conformation change in gp120 that enables the antibody binding domain to interact with a previously unexposed, conserved epitope. In addition, an antibody to CCR5 (PRO140), the HIV co-receptor, will be produced as a plantibody so that a receptor-targeted strategy can be evaluated. These HIV plantibodies and plantibody hybrids can be combined with plantibodies against other sexually transmitted disease pathogens already being produced in plants by Epicyte for broad-spectrum vaginal protection. PROPOSED COMMERCIAL APPLICATION: Plant-based production systems offer a unique opportunity to provide large quantities of protective plantibodies and plantibody hybrids at a cost that enables the application of this technology to preventing mucosal transmission of a wide range of infectious pathogens.